Date

April 2012

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

The marine environment is a rich source for chemical and biological diversity. Many marine animals are closely associated with symbiotic bacteria. Marine animals have been shown to contain natural products with complex structure and interesting pharmacological activities. These compounds are usually produced within the animal to perform a certain function relevant to the holobiont. These natural products are often synthesized by the bacteria using dedicated biosynthetic enzymes. Thus, genome analysis of microbes can predict the potential for the production of natural products. I analyzed the genomes of four symbionts of the shipworms Bankia gouldi and B. setacea, in addition to the metagenome of B. setacea. They all showed high potential for the production of active secondary metabolites, especially polyketides and nonribosomal peptides. One of these bacterial symbionts, Teredinibacter turnerae T7901, was subjected to an antibacterial-guided fractionation to yield two compounds. Analysis of these compounds using 1 and 2D nuclear magnetic resonance spectrometry, in addition to mass spectrometry, led to their structure elucidation. These two compounds belonged to the macrodiolide polyketides, tartrolons. The biosynthetic gene cluster of this group was identified using gene disruption mutation and analysis and a biosynthetic scheme was proposed. Tartrolons are prevalent in other T. turnerae strains and are found to be expressed in the shipworm host suggesting an important function. I propose that tartrolons might be playing a role in the regulation of the boron levels in the animal, in addition to the inhibition of specific bacteria within the shipworm. Tartrolon E was found to be active against pathogenic bacteria. Another system that involves a potential symbiotic relationship is associated with the ascidian Ecteinascidia and is based on the anticancer compound Et743. A survey on different Ecteinascidia animals from different geographical locations was performed, using high resolution mass spectrometry and polymerase chain reaction to establish the presence of Et743, in addition to potential gene fragments that could be involved in the biosynthesis of the compound in these populations. The study of natural products produced by symbiotic bacteria within marine invertebrates could provide a rich source for biologically active compounds. Moreover, the study of their biosynthetic gene clusters could lead to the heterologous expression of these pathways to produce higher amounts or to the formation of combinatorial biosynthetic analogs of higher activity and/or less toxicity.

Identifier

doi:10.6083/M4D798D2

Division

Div. of Environmental & Biomolecular Systems

School

School of Medicine

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.